The Molecular Mechanism Involved In The Usage Of Optogenetic Stimulation To Promote Functional Recovery In The Lateral Amygdala After Ischemic Stroke

Cerebral Ischemic Stroke(CIS)is a cerebrovascular disease currently with a high incidence rate,high morbidity,and high recurrence rate.It is also one of the three greatest causes of death in people worldwide.Ischemic stroke is caused mainly by vascular occlusion and decreased cerebral blood flow,which causes neuronal death due to insufficient energy supplies.Currently,there are no effective drug treatments for CIS.However,previous study indicates that after a stroke,ischemia areas can promote recovery of function by increasing neuronal excitation in associated pathways.In this study,first promoting ischemic stroke using the photo thrombosis method,then assess the molecular mechanisms which aid brain recovery.Through this methods,hoping to relate this model with clinical treatments of stroke patients to promote their recovery.There are a variety of methods to stimulate brain regions such as Deep Brain Stimulation(DBS)and Transcranial Magnet Stimulation(TMS)to regulate excitability in the target area.However,with advancements in the field of optogenetics,we are able to regulate excitability in certain areas with even more precision.Therefore,we hope in our research to provide new ideas and a strong theoretical basis of the possibility of using optogenetics as a clinical treatment of CIS.In current study,using photo thrombosis to selectively induce ischemia in the auditory cortex-lateral amygdala pathway.Then stimulate the external capsule using a standard 100 Hz stimulation and record in the lateral amygdala.Injecting an optogenetic virus in vivo,which allows selective regulation of the postsynaptic excitability between the auditory cortex and lateral amygdala,promoting functional recovery in the LA from ischemia.Exploring the molecular mechanisms involved in recovery of the auditory cortex-LA pathway using optogenetics can provide new therapeutic techniques to regain function after stroke.The study find that photothrombosis can cause ischemia in the LA of rats without any evidence of self-recovery within one week.Ischemia in the LA region affects the acquisition and retrieval of fear conditioning associated with auditory stimuli,but does not affect overall fear-related memory formation.An optogenetic virus was expressed specifically in the auditory cortex and along axons projecting to the LA.Under physiological conditions,100 Hz high frequency stimulation of the EC-LA pathway induced NMDA receptor-dependent LTP.However,in rats with ischemia,this pathway is blocked.Optogenetic stimulation of the LA region causes recovery of ischemia,which then also recovers synaptic plasticity of the LA region.NMDA receptors,calcium ions,and mGluR are necessary for recovery.